Valérie Mongrain

Centre de recherche de l'Hôpital du Sacré-Coeur de Montréal

Domaine : neurosciences, santé mentale et toxicomanies

Programme chercheurs-boursiers - Junior 2

Concours 2015-2016

Abstract

Sleep loss impacts mood, vigilance and learning. Sleep alterations in psychiatric/neurological conditions can therefore exacerbate brain dysfunctions. Data suggests that this depends on the impact of sleep loss on synapses (i.e., functional units of neuronal cell communication). Also, changes in cognition after sleep loss appear to originate from modifications in gene expression (i.e., the reading of a gene expressed as a transcript). In cells, including neurons, gene expression happens in the nucleus.

The general aim of this program is to understand mechanisms regulating gene expression within the nucleus that affect synaptic elements as a function of wakefulness duration using experiments in mice. Furthermore, the program aims to understand the contribution of this nuclear-synaptic dialogue to memory and sleep intensity (i.e., slow brain electrical activity). This will be achieved using four research axes. The first two will investigate the contribution of two synaptic elements (i.e., Neuroligin-1 and EphA4) to two different sleep regulatory processes (i.e., recovery and circadian regulation). Meanwhile, these axes will verify the contribution of clock elements to the gene expression of Neuroligin-1 and EphA4 using in vivo (in mice) and in vitro (assays with cells in culture) methodologies. A third axis will establish the contribution of two epigenetic marks to wakefulness/sleep-dependent changes in memory and sleep intensity using a genome-wide approach. Targeted epigenetic marks are stable DNA modifications importantly involved in the regulation of gene expression, including those regulating synapses. Lastly, the contribution of these mechanisms to brain recovery in a clinical context will be established using sleep recording after traumatic brain injury in mice not expressing synaptic elements (i.e., Neuroligin-1 and EphA4). The results will advance understanding of brain functioning and assist the development of interventions for people suffering from sleep alterations, including age-related disturbances, insomnia and traumatic brain injury.